Dai Qin, Wei Jinfei, Li Ziwei, Li Ting, Fang Yenan, Li Xinyu, Shen Bingyan, Xie Qiqi, Wang Min, Wu Wencan
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
J Neurooncol. 2025 Apr;172(2):377-386. doi: 10.1007/s11060-024-04918-6. Epub 2025 Jan 3.
This study explores the effects of mifepristone on the proliferation, motility, and invasion of malignant and benign meningioma cells, aiming to identify mifepristone-sensitive types and investigate the underlying molecular mechanisms.
IOMM-Lee and HBL-52 meningioma cells were treated with 0, vehicle control (VC), 5, 10, 20, 40, and 80 μM of mifepristone for 12, 24, 48, 72, and 96 h. Proliferation was assessed via CCK8 assay, while motility and invasion were measured using wound scratch and transwell assays. RNA sequencing and RT-PCR were used to analyze gene expression changes.
Mifepristone inhibited proliferation, motility, and invasion in both IOMM-Lee and HBL-52 cells in a dose- and time-dependent manner. RNA sequencing showed up-regulated genes significantly enriched in the ferroptosis pathway in both cell lines, confirmed by increased p53 and HO1 expression, decreased GPX4 expression, lipid peroxidation, Fe accumulation, and ROS release. Immunofluorescence staining and RT-PCR also revealed a corresponding decrease in mifepristone-related progesterone receptor expression.
Mifepristone induces ferroptosis in meningioma cells via the PR/p53/HO1/GPX4 axis, suggesting its potential as a treatment for ferroptosis-sensitive meningiomas. It also supplies new clues regarding ferroptosis as a treatment entry point for meningiomas.
本研究探讨米非司酮对恶性和良性脑膜瘤细胞增殖、运动及侵袭的影响，旨在确定对米非司酮敏感的类型并研究其潜在分子机制。
用0、溶剂对照（VC）、5、10、20、40和80μM米非司酮处理IOMM-Lee和HBL-52脑膜瘤细胞12、24、48、72和96小时。通过CCK8法评估增殖，使用划痕实验和Transwell实验测量运动和侵袭。采用RNA测序和RT-PCR分析基因表达变化。
米非司酮对IOMM-Lee和HBL-52细胞的增殖、运动和侵袭均有剂量和时间依赖性抑制作用。RNA测序显示两种细胞系中上调基因在铁死亡途径中显著富集，p53和HO1表达增加、GPX4表达降低、脂质过氧化、铁积累和活性氧释放增加证实了这一点。免疫荧光染色和RT-PCR也显示米非司酮相关孕酮受体表达相应降低。
米非司酮通过PR/p53/HO1/GPX4轴诱导脑膜瘤细胞铁死亡，提示其作为铁死亡敏感型脑膜瘤治疗药物的潜力。它也为铁死亡作为脑膜瘤治疗切入点提供了新线索。
